Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics

Hand‐foot‐skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand‐foot‐skin reaction in a child taking sorafenib for an unresectable desmoid tumor.     

Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing.     

Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing

Superoxide is the single-electron reduction product of molecular oxygen generated by mitochondria and the innate immune enzyme complex, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and its isoforms. Initially identified as critical to the host defense against infection, superoxide has recently emerged as an important signaling molecule and as a proposed mediator of central nervous system injury in stroke, neurodegenerative conditions, and aging itself. Complete understanding of superoxide in central nervous system disease has been hampered by lack of noninvasive imaging techniques to evaluate this highly reactive, short-lived molecule in vivo. Here we describe a novel optical imaging technique to monitor superoxide real time in intact animals using a fluorescent probe compound and fluorescence lifetime contrast-based unmixing. Specificity for superoxide was confirmed using validated mouse models with enhanced or attenuated brain superoxide production. Application of fluorescence lifetime unmixing removed autofluorescence, further enhanced sensitivity and specificity of the technique, permitted visualization of physiologically relevant levels of superoxide, and allowed superoxide in specific brain regions (e.g., hippocampus) to be mapped. Lifetime contrast-based unmixing permitted disease model-specific and brain region-specific differences in superoxide levels to be observed, suggesting this approach may provide valuable information on the role of mitochondrial and Nox-derived superoxide in both normal function and pathologic conditions in the central nervous system.     

A Study on the Extraction and Purification Process of Lily Polysaccharide and Its Anti-Tumor Effect

The objective of this paper was to extract and purify lily polysaccharide and to study its anti-H22 hepatoma effect in mice. Orthogonal experimental method was used to analyze the factors influencing the extraction and purification of lily polysaccharide, and the anti-tumor effect of lily polysaccharide was studied by acting it on H22-bearing mice. The results showed that the size of influence of various factors on the extraction results of lily polysaccharide were extraction time, extraction times and extraction temperature in decreasing order. Lily polysaccharide can enhance the immune function of H22 tumor-bearing mice, and inhibit the growth of H22 tumor. The study concluded that the optimal conditions for the extraction and purification of lily polysaccharide should be extraction times of 3 times, an extraction time of 4 h each, and an extraction temperature of 60°C; lily polysaccharide has an anti-tumor effect.     

Comparison of Four Commercial One-Dose Porcine Circovirus Type 2 (PCV2) Vaccines Administered to Pigs Challenged with PCV2 and Porcine Reproductive and Respiratory Syndrome Virus at 17 Weeks Postvaccination To Control Porcine Respiratory Disease Complex under Korean Field Conditions

Under Korean field conditions, coinfection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is most commonly observed in porcine respiratory disease complex (PRDC). Despite the wide use of PCV2 vaccination, PRDC remains a serious respiratory problem. Thus, the objective of this study was to determine and compare the efficacy of 4 one-dose PCV2 vaccines on 3-week-old pigs with an experimental PCV2-PRRSV challenge at 17 weeks postvaccination. Regardless of which commercial PCV2 vaccine was used, the vaccination of piglets at 3 weeks of age was efficacious against cochallenge of PCV2 and PRRSV, on the basis of growth performance and PCV2-associated lesions. However, the inactivated chimeric PCV1-2 and the PCV2 vaccines induced higher PCV2-specific neutralizing antibody (NA) titers and PCV2-specific gamma interferon-secreting cells and lower PCV2 viremia levels than the two PCV2 subunit vaccines. The vaccination of piglets against PCV2 at 3 weeks of age was effective in reducing PCV2 viremia and PCV2-associated lesions during the finishing period, which is an age at which pigs are frequently affected by PRDC caused by coinfection with PCV2 and PRRSV under Korean field conditions.     

Intravenous Lipid Emulsion Improves Recovery Time and Quality from Isoflurane Anaesthesia: A Double‐Blind Clinical Trial

Recovery time and quality after general anaesthesia is important for patient safety. This study aimed to determine whether intravenous lipid emulsion could improve recovery profiles from isoflurane anaesthesia in adult patients undergoing laparoscopic cholecystectomy. Sixty‐six patients were enrolled. After anaesthesia induction, inspired isoflurane concentration was adjusted to maintain stable vital signs and the suitable conditions for operation. At the end of the operation, the isoflurane was discontinued, and either 2 ml/kg 30% lipid emulsions or 0.9% saline solution was administered intravenously. The time to eye opening, extubation and exit from the operation room was recorded, and the quality of recovery from anaesthesia was assessed. Sixty patients completed the study. The median time to eye opening and exit from the operation room was significantly shorter in the lipid emulsion group than in the saline group [15.5 (interquartile range 9.0) versus 20.0 (10.0) min., p = 0.01; 19.5 (8.3) versus 23.6 (6.3) min., p = 0.04, respectively], whereas the median time to extubation did not show any noticeable difference. The quality of recovery was better in the lipid emulsion group than that of the saline solution group with respect to drowsiness visual analogue scale score (p < 0.01), Observer's Assessment of Alertness/Sedation score (p < 0.01), Mini‐Mental State Examination score (p = 0.04) and Modified Aldrete Post Anaesthesia Recovery score (p = 0.03). No serious adverse events were observed during the study period. In conclusion, intravenous lipid emulsion may effectively improve the recovery time and quality from isoflurane anaesthesia for laparoscopic cholecystectomy.     

Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation,clot retraction,and in vivo thrombosis formation

Protein arginylation by arginyl–transfer RNA protein transferase (ATE1) is emerging as a regulator protein function that is reminiscent of phosphorylation. For example, arginylation of β-actin has been found to regulate lamellipodial formation at the leading edge in fibroblasts. This finding suggests that similar functions of β-actin in other cell types may also require arginylation. Here, we have tested the hypothesis that ATE1 regulates the cytoskeletal dynamics essential for in vivo platelet adhesion and thrombus formation. To test this hypothesis, we generated conditional knockout mice specifically lacking ATE1 in their platelets and in their megakaryocytes and analyzed the role of arginylation during platelet activation. Surprisingly, rather than finding an impairment of the actin cytoskeleton structure and its rearrangement during platelet activation, we observed that the platelet-specific ATE1 knockout led to enhanced clot retraction and in vivo thrombus formation. This effect might be regulated by myosin II contractility since it was accompanied by enhanced phosphorylation of the myosin regulatory light chain on Ser19, which is an event that activates myosin in vivo. Furthermore, ATE1 and myosin co-immunoprecipitate from platelet lysates. This finding suggests that these proteins directly interact within platelets. These results provide the first evidence that arginylation is involved in phosphorylation-dependent protein regulation, and that arginylation affects myosin function in platelets during clot retraction.